Circular RNAs regulate signal transducer and activator of transcription 3 signaling pathway to drive cancer therapy resistance.
Cancer therapy resistance remains a major challenge to effective cancer treatment, leading to disease progression and patient deterioration. The STAT3 signaling pathway is a well-known central hub that promotes cancer progression and treatment resistance. Interestingly, circRNAs have recently been identified as key regulators of STAT3 signaling in cancer therapy resistance. Therefore, in this review, we highlight current knowledge concerning the molecular functions of circRNAs in regulating cancer therapy resistance via the STAT3 signaling pathway. We describe how circRNAs aberrantly stimulate or suppress cancer therapy resistance by acting as protein recruiters, protein scaffolds, miRNA sponges, and templates for peptide translation. In addition, we comprehensively discuss the evidence supporting the role of the circRNA/STAT3 axis in resistance to immunotherapy, chemotherapy, and radiotherapy in a variety of malignancies. Finally, we address how exosomal circRNAs mediate STAT3-driven resistance via intercellular communication. Understanding these mechanisms offers important insights into novel therapeutic targets for overcoming treatment resistance in cancer, as well as potential diagnostic biomarkers based on circRNAs.